NRG1_CHICK
ID NRG1_CHICK Reviewed; 602 AA.
AC Q05199; O73750; O73751; O73752;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Pro-neuregulin-1, membrane-bound isoform;
DE Short=Pro-NRG1;
DE Contains:
DE RecName: Full=Neuregulin-1;
DE AltName: Full=Acetylcholine receptor-inducing activity;
DE Short=ARIA;
DE Flags: Precursor;
GN Name=NRG1; Synonyms=ARIA;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP FUNCTION.
RC STRAIN=White leghorn; TISSUE=Brain;
RX PubMed=8453670; DOI=10.1016/0092-8674(93)90407-h;
RA Falls D.L., Rosen K.M., Corfas G., Lane W.S., Fischbach G.D.;
RT "ARIA, a protein that stimulates acetylcholine receptor synthesis, is a
RT member of the neu ligand family.";
RL Cell 72:801-815(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), AND FUNCTION.
RC TISSUE=Brain, and Spinal cord;
RX PubMed=9491987; DOI=10.1016/s0896-6273(00)80454-7;
RA Yang X., Kuo Y., Devay P., Yu C., Role L.;
RT "A cysteine-rich isoform of neuregulin controls the level of expression of
RT neuronal nicotinic receptor channels during synaptogenesis.";
RL Neuron 20:255-270(1998).
CC -!- FUNCTION: Direct ligand for the ERBB tyrosine kinase receptors. The
CC multiple isoforms perform diverse functions: cysteine-rich domain
CC containing isoforms (isoform 2-isoform 4) probably regulate the
CC expression of nicotinic acetylcholine receptors at developing
CC interneuronal synapses. Isoform Ig-NRG is required for the initial
CC induction and/or maintenance of the mature levels of acetylcholine
CC receptors at neuromuscular synapses (PubMed:8453670, PubMed:9491987).
CC Binds to ERBB3 and integrins to form a complex which is essential for
CC NRG1-ERBB signaling (By similarity). {ECO:0000250|UniProtKB:Q02297,
CC ECO:0000269|PubMed:8453670, ECO:0000269|PubMed:9491987}.
CC -!- SUBCELLULAR LOCATION: [Pro-neuregulin-1, membrane-bound isoform]: Cell
CC membrane {ECO:0000250}; Single-pass type I membrane protein
CC {ECO:0000250}. Note=Does not seem to be active. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Neuregulin-1]: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=ARIA, Ig-NRG;
CC IsoId=Q05199-1; Sequence=Displayed;
CC Name=2; Synonyms=CRD-NRG-BETA1A;
CC IsoId=Q05199-2; Sequence=VSP_003445;
CC Name=3; Synonyms=CRD-NRG-BETA2A;
CC IsoId=Q05199-3; Sequence=VSP_003445, VSP_003446;
CC Name=4; Synonyms=CRD-NRG-BETA2B;
CC IsoId=Q05199-4; Sequence=VSP_003445, VSP_003446, VSP_003447,
CC VSP_003448;
CC -!- DEVELOPMENTAL STAGE: Isoform 2-isoform 4 are detected at embryonic day
CC 4 (ED4) in both visceral and somatic motor neurons of spinal cord and
CC is highest at ED6. Isoform 1 is not expressed until ED 6 in spinal
CC cord. At ED 11 both isoforms display comparable levels.
CC -!- DOMAIN: The cytoplasmic domain may be involved in the regulation of
CC trafficking and proteolytic processing. Regulation of the proteolytic
CC processing involves initial intracellular domain dimerization (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: ERBB receptor binding is elicited entirely by the EGF-like
CC domain.
CC -!- PTM: Proteolytic cleavage close to the plasma membrane on the external
CC face leads to the release of the soluble growth factor form.
CC -!- PTM: Extensive glycosylation precedes the proteolytic cleavage.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 1]: Contains an Ig-like domain.
CC -!- MISCELLANEOUS: [Isoform 2]: The EGF-like domain is replaced by a
CC cysteine-rich domain (CRD). {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: The EGF-like domain is replaced by a
CC cysteine-rich domain (CRD). {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: The EGF-like domain is replaced by a
CC cysteine-rich domain (CRD). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the neuregulin family. {ECO:0000305}.
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DR EMBL; L11264; AAA49037.1; -; mRNA.
DR EMBL; AF045654; AAC05670.1; -; mRNA.
DR EMBL; AF045655; AAC05671.1; -; mRNA.
DR EMBL; AF045656; AAC05672.1; -; mRNA.
DR PIR; A45769; A45769.
DR RefSeq; NP_989448.1; NM_204117.1. [Q05199-2]
DR RefSeq; XP_015135889.1; XM_015280403.1. [Q05199-3]
DR AlphaFoldDB; Q05199; -.
DR IntAct; Q05199; 1.
DR STRING; 9031.ENSGALP00000024830; -.
DR PaxDb; Q05199; -.
DR GeneID; 373906; -.
DR KEGG; gga:373906; -.
DR CTD; 3084; -.
DR VEuPathDB; HostDB:geneid_373906; -.
DR eggNOG; ENOG502QRUM; Eukaryota.
DR HOGENOM; CLU_023628_1_0_1; -.
DR InParanoid; Q05199; -.
DR OrthoDB; 313400at2759; -.
DR PhylomeDB; Q05199; -.
DR PRO; PR:Q05199; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0038127; P:ERBB signaling pathway; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR040180; Neuregulin.
DR InterPro; IPR002154; Neuregulin_C.
DR InterPro; IPR018250; NRG1.
DR PANTHER; PTHR11100; PTHR11100; 2.
DR PANTHER; PTHR11100:SF25; PTHR11100:SF25; 2.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF02158; Neuregulin; 1.
DR PRINTS; PR01089; NEUREGULIN.
DR SMART; SM00181; EGF; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Growth factor;
KW Immunoglobulin domain; Membrane; Reference proteome; Secreted;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..602
FT /note="Pro-neuregulin-1, membrane-bound isoform"
FT /id="PRO_0000019468"
FT CHAIN 1..205
FT /note="Neuregulin-1"
FT /id="PRO_0000019469"
FT TOPO_DOM 1..206
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..229
FT /note="Helical; Note=Internal signal sequence"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..602
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 29..123
FT /note="Ig-like C2-type"
FT DOMAIN 137..181
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 293..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 486..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 294..350
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 519..535
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..105
FT /evidence="ECO:0000250"
FT DISULFID 141..155
FT /evidence="ECO:0000250"
FT DISULFID 149..169
FT /evidence="ECO:0000250"
FT DISULFID 171..180
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..127
FT /note="MWATSEGPLQYSLAPTQTDVNSSYNTVPPKLKEMKNQEVAVGQKLVLRCETT
FT SEYPALRFKWLKNGKEITKKNRPENVKIPKKQKKYSELHIYRATLADAGEYACRVSSKL
FT GNDSTKASVIITDTNA -> MSEVGTETFPSPSAQLSPDASLGGLPAEENMPGPHREDS
FT RVPGVAGLASTCCVCLEAERLKGCLNSEKICIAPILACLLSLCLCIAGLKWVFVDKIFE
FT YDSPTHLDPGRIGQDPRSTVDPTALSAWVPSEVYASPFPIPSLESKAEVTVQTDSSLVP
FT SRPFLQPSLYNRILDVGLWSSATPSLSPSSLEPTTASQAQATETNLQTAPKLS (in
FT isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:9491987"
FT /id="VSP_003445"
FT VAR_SEQ 191..198
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:9491987"
FT /id="VSP_003446"
FT VAR_SEQ 388..405
FT /note="VSAMTTPARMSPVDFHTP -> HTPPTSLLLAGKVSLRVS (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:9491987"
FT /id="VSP_003447"
FT VAR_SEQ 406..602
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9491987"
FT /id="VSP_003448"
SQ SEQUENCE 602 AA; 67454 MW; 4183C0E56CE5D346 CRC64;
MWATSEGPLQ YSLAPTQTDV NSSYNTVPPK LKEMKNQEVA VGQKLVLRCE TTSEYPALRF
KWLKNGKEIT KKNRPENVKI PKKQKKYSEL HIYRATLADA GEYACRVSSK LGNDSTKASV
IITDTNATST STTGTSHLTK CDIKQKAFCV NGGECYMVKD LPNPPRYLCR CPNEFTGDRC
QNYVMASFYK HLGIEFMEAE ELYQKRVLTI TGICIALLVV GIMCVVAYCK TKKQRKKLHD
RLRQSLRSER NNVMNMANGP HHPNPPPDNV QLVNQYVSKN IISSERVVER ETETSFSTSH
YTSTTHHSMT VTQTPSHSWS NGHTESILSE SHSVLVSSSV ENSRHTSPTG PRGRLNGIGG
PREGNSFLRH ARETPDSYRD SPHSERYVSA MTTPARMSPV DFHTPTSPKS PPSEMSPPVS
SLTISIPSVA VSPFMDEERP LLLVTPPRLR EKYDNHLQQF NSFHNNPTHE SNSLPPSPLR
IVEDEEYETT QEYEPAQEPP KKLTNSRRVK RTKPNGHISS RVEVDSDTSS QSTSSESETE
DERIGEDTPF LSIQNPMATS LEPAAAYRLA ENRTNPANRF STPEELQARL SSVIANQDPI
AV
